(1) Field of Invention
The present invention relates to a conjugated peptide for conferring protection against autoimmune diseases, such as, for example, myocarditis and autoimmune thyroid disease, allergic diseases, asthma, host-versus graft and graft-versus-host disease. The present invention also relates to a method for treating or inhibiting development of autoimmune diseases, asthma, allergy, and tissue transplantation rejection and to conjugated peptides and compositions which may be used to carry out said method.
(2) Background of the Invention
A technique for modulating T cell immunological responses to a wide range of antigenic peptides has been described in the literature. This technology, referred to as LEAPS™, provides conjugated peptide immunogens (constructs) that modulate both cellular and humoral responses to treat/prevent major diseases, such as HIV infection, herpes simplex virus (HSV) infection, tuberculosis, and the like. The LEAPS constructs are conjugates of two peptides which are linked together covalently. One peptide of the conjugate is an antigen-specific epitope which will bind to the T cell receptor upon recognition. The other peptide of the conjugate is a T cell binding ligand (TCBL) derived from molecules with a known activity, such as, for example, β-2 microglobulin, IL-1, IL-2, or nonpolymorphic MHC regions, (hereinafter may be referred to as Peptide P2) and which will engage other sites on the T cells to promote activation of a particular set or subset of T cells. A more detailed discussion of the LEAPS™ technology can be found in the commonly assigned U.S. Pat. No. 5,652,342, to Zimmerman, et al., the disclosure of which is incorporated herein in its entirety by reference thereto.
Briefly, the LEAPS technology allows for the preferential presentation of antigen(s) (peptide sequences) to antigen presenting cells, lymphocytes (T and B cells), dendritic cells, and other cells of the immune system. The antigen presentation is directed in such a way as to affect immune response outcome and determine with some certainty the type of immune response outcome, humoral or cellular. Thus, with the use of certain combinations of appropriate T cell binding peptide molecules together with the appropriate antigen, or the pathogenic molecule(s) of a complex antigen, forming the LEAPS construct, a cellular, antibody, or a mixed immune response can be induced by administration of the LEAPS construct.
While the LEAPS conjugates studied to date were designed to activate the T-cell immunological response to a disease causing antigen, there is also a suggestion in the aforementioned U.S. Pat. No. 5,652,342, that the LEAPS conjugated peptides can activate T suppressor cells or a subset of T suppressor cells, by selection of an appropriate TCBL which will selectively activate, for example, a subset of T suppressor cells.